The Biochemistry area of the Laboratory of Toxicology is engaged in the study of L-asparagine synthetase from murine leukemic cells and normal pancreas. A systematic search is underway for agents able to inhibit the tumoral enzyme, selectively. Among the promising candidates are mucochloric and mucobromic acids, maleimide (and other sulfhydryl reagents) and the diazoketone analogues of L-glutamine; L-DON, L-DONV, and L-CONV. Attempts to isolate L-asparagine synthetase from L5178Y/AR cells have succeeded in yielding a thousand-fold purification, but the enzyme becomes progressively unstable as its purity increases. Studies to determine the influence of the subject inhibitors on the concentration and biosynthesis of L-asparagine in vivo are also underway; in many cases, agents which inhibit in vitro are apparently inert in vivo. A pharmacologic explanation for this discrepancy is being sought.